Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen–glucose-deprivation in organotypic hippocampal slice cultures

Martinez-Sanchez, Monica; Striggow, Frank; Schröder, Ulrich H.; Kahlert, Stefan; Reymann, Klaus G.; Reiser, Georg

doi:10.1016/j.neuroscience.2004.06.074

Cited by 78 publications

(73 citation statements)

References 44 publications

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“…Inhibitors of AMPA and NMDA cation channels, as well as sodium channel blockers and antioxidants, were found to attenuate edema formation in earlier studies (LoPachin et al, 2001;MacGregor et al, 2003). The importance of sodium and calcium influx for ischemia-induced edema formation and cellular injury was also documented in organotypical slice cultures exposed to OGD (Breder et al, 2000;Martinez-Sanchez et al, 2004) and in neuronal cell cultures (Goldberg and Choi, 1993;Czyz et al, 2002).…”

Section: Introductionmentioning

confidence: 91%

Effects of chloride flux modulators in an in vitro model of brain edema formation

et al. 2006

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Brain edema is a serious consequence of hemispheric stroke and traumatic brain injury and contributes significantly to patient mortality. In the present study, we measured water contents in hippocampal slices as an in vitro-model of edema formation. Excitotoxic conditions induced by Nmethyl-D-aspartate (NMDA, 300 μM), as well as ischemia induced by oxygen-glucose deprivation (OGD) caused cellular edema formation as indicated by an increase of slice water contents. In the presence of furosemide, an inhibitor of the Na,K,Cl-cotransporter, NMDA-induced edema were reduced by 64% while OGD-induced edema were unaffected. The same observation, i.e. reduction of excitotoxic edema formation but no effect on ischemia-induced edema, was made with chloride transport inhibitors such as DIDS and niflumic acid. Under ischemic conditions, modulation of GABA A receptors by bicuculline, a GABA antagonist, or by diazepam, a GABAergic agonist, did not significantly affect edema formation. Further experiments demonstrated that low chloride conditions prevented NMDA-induced, but not OGD-induced water influx. Omission of calcium ions had no effect. Our results show that NMDA-induced edema formation is highly dependent on chloride influx as it was prevented by low-chloride conditions and by various compounds that interfere with chloride influx. In contrast, OGD-induced edema observed in brain slices were not affected by modulators of chloride fluxes. The results are discussed with reference to ionic changes occurring during tissue ischemia.Section: Neurophysiology, Neuropharmacology and other forms of Intercellular Communication.

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Section: Introductionmentioning

confidence: 91%

Effects of chloride flux modulators in an in vitro model of brain edema formation

et al. 2006

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“…Activation of NMDA receptors plays a role in neuronal death induced by transient OGD in different neuronal culture systems (Martinez-Sanchez et al, 2004;Bonde et al, 2005;Ahlgren et al, 2011;Caldeira et al, 2013), similarly to the role of glutamate receptors in neuronal damage in the ischemic brain [for review (Kostandy, 2012)]. The activation of NMDA-type glutamate receptors is likely to be a mediator in OGD and ischemia-induced downregulation of the proteasome activity, as shown in experiments where cultured hippocampal neurons were subjected to excitotoxic stimulation with glutamate or with NMDA (Caldeira et al, 2013).…”

Section: Ups In Glutamate-induced Excitotoxicitymentioning

confidence: 99%

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Caldeira

Salazar

Curcio

et al. 2014

Progress in Neurobiology

117

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A B S T R A C TThe ubiquitin-proteasome system (UPS) is a catalytic machinery that targets numerous cellular proteins for degradation, thus being essential to control a wide range of basic cellular processes and cell survival. Degradation of intracellular proteins via the UPS is a tightly regulated process initiated by tagging a target protein with a specific ubiquitin chain. Neurons are particularly vulnerable to any change in protein composition, and therefore the UPS is a key regulator of neuronal physiology. Alterations in UPS activity may induce pathological responses, ultimately leading to neuronal cell death. Brain ischemia triggers a complex series of biochemical and molecular mechanisms, such as an inflammatory response, an exacerbated production of misfolded and oxidized proteins, due to oxidative stress, and the breakdown of cellular integrity mainly mediated by excitotoxic glutamatergic signaling. Brain ischemia also damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated proteins, contribute to the accumulation of ubiquitincontaining proteinaceous deposits. Despite recent advances, the factors leading to deposition of such aggregates after cerebral ischemic injury remain poorly understood. This review discusses the current knowledge on the role of the UPS in brain function and the molecular mechanisms contributing to UPS dysfunction in brain ischemia with consequent accumulation of ubiquitin-containing proteins. Chemical inhibitors of the proteasome and small molecule inhibitors of deubiquitinating enzymes, which promote the degradation of proteins by the proteasome, were both shown to provide neuroprotection in brain ischemia, and this apparent contradiction is also discussed in this review. ß

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“…Although the contribution of changes in intracellular Ca 2ϩ (Ca 2ϩ i ) has received particular attention, notably within the framework of the excitotoxic model of injury, early increases in intracellular Na ϩ (Na ϩ i ) also occur and contribute to the pathophysiology of neuronal death (Lipton, 1999;Martinez-Sánchez et al, 2004). Sodium influx increases the demand for cellular ATP to maintain the Na ϩ gradient (Chinopoulos et al, 2000) and may contribute to neuronal injury by promoting, for example, the following: membrane depolarization (Haddad and Jiang, 1993;Calabresi et al, 1999), neuronal swelling (Goldberg and Choi, 1993;Chidekel et al, 1997), reverse-mode glutamate reuptake (Roettger and Lipton, 1996), cytosolic Ca 2ϩ accumulation via reverse-mode Na ϩ / Ca 2ϩ exchange and/or impaired mitochondrial Ca 2ϩ uptake (Zhang and Lipton, 1999;Breder et al, 2000;Czyż et al, 2002), Na ϩ i -dependent increases in NMDA receptor-mediated responses (Yu and Salter, 1998;Manzerra et al, 2001), and the activation of second-messenger pathways (Cooper et al, 1998;Hayasaki-Kajiwara et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Sheldon

Diarra²,

Cheng³

et al. 2004

J. Neurosci.

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Mechanisms that contribute to Na ϩ influx during and immediately after 5 min anoxia were investigated in cultured rat hippocampal neurons loaded with the Na ϩ -sensitive fluorophore sodium-binding benzofuran isophthalate. -dependent mechanism(s). The results provide insight into the intrinsic mechanisms that contribute to disturbed internal Na ϩ homeostasis during and immediately after anoxia in rat hippocampal neurons and, in this way, may play a role in the pathogenesis of anoxic or ischemic cell injury.

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Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen–glucose-deprivation in organotypic hippocampal slice cultures

Cited by 78 publications

References 44 publications

Effects of chloride flux modulators in an in vitro model of brain edema formation

Effects of chloride flux modulators in an in vitro model of brain edema formation

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

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